BMJ, July 26, 2008
Should we screen for childhood dyslipidemia?
The obesity epidemic raises the stakes for using statins in children
It is not an accident that evidence-based guidelines more or less began with clinical preventive services. Unlike treatment for problems that produce symptoms, preventive medicine is optional. We have the luxury of time to gather and evaluate the evidence for the efficacy and even effectiveness* of screening tests and counseling. When someone rushes into a doctor’s office bleeding or doubled over in pain, it would hardly be acceptable to send them away untreated to await the results of a randomized controlled trial for their problem. But that is just what doctors should do when people want to know whether they should undergo computed tomography to screen for lung cancer or be given vitamins to prevent heart disease. “Sorry,” good doctors say, “insufficient evidence.”
And this is even truer for children—at least when the question is whether to screen them for early signs or symptoms of adult diseases. First, we need to know whether the problem will even persist into adulthood. Second, do we have a safe and effective treatment? Third and most importantly, does treating the problem in childhood have any effect on clinical outcomes in adulthood?
Which brings us to the case of high blood cholesterol levels—technically, dyslipidemia—in childhood. New guidelines for screening and treatment from the American Academy of Pediatrics have caused a lot of controversy. The pediatricians recommend screening with a fasting lipid profile every 3 to 5 years for all children aged 2 to 10 years who are overweight or have diabetes or a family history of cardiovascular disease. It is reasonable to ask, especially as the epidemic of childhood overweight and obesity has increased the number of children who will be screened, what this screening will accomplish.
* “Efficacy” is whether a test or a treatment works in a clinical trial done in a specialized setting; “effectiveness” is whether it works in the real world of everyday care.
Does heart disease start in childhood? It probably does, as autopsies of children who die from other causes have found. And some studies have correlated autopsy findings with dyslipidemia in children. So it would be nice to try to identify children who are at risk of developing heart disease, assuming that we could find them and actually do something that would make a difference when they are adults. But there are a number of problems.
One is that lipid measurement in children is not a perfect marker for present or future heart disease. Lipid concentrations vary during childhood, especially around puberty. They also vary with gender and race. And they don’t “track” into adulthood perfectly: somewhere between 30 percent and 50 percent of children with raised cholesterol concentrations won’t have them as adults.
A further problem is the treatment for children with raised lipids. Exercise and diet management work, but only in research settings. It’s very hard in the real world to get an individual child to eat better, exercise more, and lose weight—and to maintain all of that until adulthood. In addition, as usual, long-term studies that follow such children until they are old enough to have cardiac-related health outcomes are almost impossibly difficult to do.
But the real controversy behind these new guidelines is drug treatment. In a striking departure from previous recommendations, the American Academy of Pediatrics endorses the use from the age of 8 of cholesterol- lowering statin drugs for children who have raised lipid concentrations that have not responded to diet, weight reduction, and exercise. Admittedly this will be a small subset of all children, but commitment to what is likely to be at least 50 years of statin treatment raises many questions.
Do statin medications lower lipid concentrations in children? Yes, they do. Short-term clinical trials of children with familial hypercholesterolemia have found statins to be safe and effective in lowering concentrations of low density lipoprotein (LDL). What about clinical outcomes? As children don’t have heart attacks, investigators have looked at the effects of statins on endothelial dysfunction and carotid intimal medial thickness, early markers for atherosclerosis in adults. Controlled studies in children show that, in comparison with control children, statins improve these. So it looks as though statins can make a difference, at least in the short term.
But what about evidence that dozens of years of statin treatment in children with raised lipids will actually improve cardiac outcomes in
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Should we screen for childhood dyslipidemia?
adulthood? That, of course, is the Holy Grail, and such data are not available. It is likely that they never will be, at least for the foreseeable future. That is a big problem.
I think the obesity epidemic really raises the stakes in this discussion. This is no longer just a discussion of what to do with a very small group of children with an autosomal dominant genetic disorder that virtually guarantees disastrous cardiac outcomes as adults. Now we are moving to mass population screening and treatment of the rapidly increasing number of fat children. Most of them will not have familial hypercholesterolemia, and doctors really don’t know what they are doing by treating them for 50 years with statins.
The obesity epidemic is real. We don’t have to just stand by and watch it progress. We can and should improve many things, including food and exercise policies in schools, the built environment, and families’ diets and physical activity. But I’m very wary of committing a generation of obese children to a lifetime of drug treatment on the basis of pathological markers for possible future disease.
This is preventive medicine, after all. Without good evidence, rather than say, “Don’t just stand there—do something,” I’d advocate the opposite.
NPR, August 5, 2008